Mind Matters - June 2007Written by Ron Sterling, M.D. and Published in Northwest Prime Time Magazine

Yellow, Pink and Blue Peopleby Ron Sterling, M.D. -- June 2007

Dear Dr. Ron:

You have written about how stress can produce major depression. I am wondering why some people can handle huge amounts of stress with no apparent depression? Is it that they learned certain skills for handling stress or do they just have better genes? Signed: Wondering About Genes.

Dear Wondering:

Thank you for writing! This is a complicated subject that is difficult to simplify, but I think I can get you started in understanding the most recent research, which has looked at a gene called the "Serotonin Transporter Gene" (hSERT). For more information and links to citations, please visit the Web sites that are listed at the end of this article.

As you may know, serotonin is an important neurotransmitter in mammalian brains. A neurotransmitter is a chemical bridge between two brain cells. There are many neurotransmitters. Generally, they often have specific functions and are limited to certain locations in the brain.

Most people are familiar with the word "serotonin" due to reading about so-called serotonin antidepressants (Prozac® and many others), which are often referred to as SSRIs (selective serotonin reuptake inhibitors). Normally, once a serotonin molecule is released to build a bridge between two or more brain cells and its function is no longer needed, it is absorbed by one of the brain cells and stored there to be used again in the future. An SSRI, like Prozac®, more-or-less blocks (inhibits) that absorption. Unfortunately, even though we know that SSRIs are helpful in treating moderate to severe depression, we do not know precisely how they produce those positive results.

It used to be thought that SSRIs worked by increasing serotonin in the brain, however, we also have discovered that SSRIs produce a healing and protective effect for a part of the brain called the hippocampus, which can be particularly vulnerable to certain "toxic" effects of chemicals produced by our physiological response to stress ("fight or flight response").

Here's the main story about the hSERT gene. It is a relatively simple gene. It comes in two types -- a long type and a short type. Since we get one of those genes from each of our parents, we can end up with one of three variations which I have given names -- (1) long-long pair (yellow), (2) long-short pair (pink), or (3) short-short pair (blue). Since we cannot study living human brain cells very well, we do not yet know exactly the role the transporter gene plays in depression. However, it is likely that a "strong" (long-long) serotonin transporter gene means that less serotonin is "lost" compared to a short-short gene which may create a serotonin transporter system that doesn't work well and loses a lot of serotonin over time. Other studies have shown that the hSERT gene controls the size of our amygdala (a brain region that controls fear responses).

One of the most significant studies on the hSERT gene was done at the University of Otago in Dunedin, New Zealand. The University has followed more than 1,000 infants since their birth in the year 1972. Science Magazine's article detailing the Dunedin hSERT study, published July 18, 2003, is entitled "Getting the Short End of the Allele."

What they found was no less than stunning. People with the yellow (long-long) genetic hSERT variation were very resistant to the harmful effects of stressful events. Among the research subjects who met the criteria for four recent stressful events (between ages 21 and 26), 43% of those with the blue gene (short-short) experienced major depression compared to 17% of those with the yellow gene (long-long). In the Dunedin study, 17% of the 847 subjects had the blue variation, 31% had the yellow variation, and 51% had the pink variation.

I think we can call the yellow hSERT variation the "resilience" gene and the blue variation the "vulnerability" gene. This study, along with many others, clearly establishes that there is a significant genetic contribution to our ability to deal with stresses. Although coping and relaxation skills are important, they can be trumped by biology. I hope that helps. -- Best wishes, Dr. Ron.

Author Bio:

Ron Sterling, M.D. is a 64 year-old General and Geriatric Psychiatrist with a private practice in Seattle. He invites you to e-mail him at with any questions about mental wellness or emotional, relationship, or aging concerns. He is the only person who reads e-mail sent to Dr. Ron. Please be assured that your questions and identities are completely confidential and protected. For more information about Dr. Ron and for resources related to senior mental health, please go to SeniorMentalHealth.org. The content offered through Mind Matters is for information only and is not intended for medical, psychiatric, or psychological diagnosis or treatment. Never disregard professional advice or delay seeking it because of something you have read in this column. Read our Disclaimer. If you wish to understand more about Dr. Sterling's potential biases in health care advocacy, please check his Conflicts of Interest Disclosure Statement